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Research Square Dec 2023Respiratory Syncytial Virus (RSV) is a leading cause of acute respiratory tract infection, with greatest impact on infants, immunocompromised individuals, and older...
Respiratory Syncytial Virus (RSV) is a leading cause of acute respiratory tract infection, with greatest impact on infants, immunocompromised individuals, and older adults. RSV prevalence decreased substantially following the implementation of non-pharmaceutical interventions to mitigate the COVID-19 pandemic but later rebounded with initially abnormal seasonality. The biological and epidemiological factors underlying this altered behavior remain poorly defined. In this retrospective cohort study, we examined RSV epidemiology, clinical severity, and genetic diversity in the years surrounding the COVID-19 pandemic. We found that changes in RSV diagnostic platforms drove increased detections in outpatient settings after 2020 and that hospitalized adults with RSV-A were at higher risk of needing intensive care than those with RSV-B. While the population structure of RSV-A remained unchanged, the population structure of RSV-B shifted in geographically distinct clusters. Mutations in the antigenic regions of the fusion protein suggest convergent evolution with potential implications for vaccine and therapeutic development.
PubMed: 38168164
DOI: 10.21203/rs.3.rs-3712859/v1 -
Microorganisms Dec 2020Respiratory viral infections represent the leading cause of hospitalization in infants and young children worldwide and the second leading cause of infant mortality.... (Review)
Review
Respiratory viral infections represent the leading cause of hospitalization in infants and young children worldwide and the second leading cause of infant mortality. Among these, Respiratory Syncytial Virus (RSV) represents the main cause of lower respiratory tract infections (LRTIs) in young children worldwide. RSV manifestation can range widely from mild upper respiratory infections to severe respiratory infections, mainly bronchiolitis and pneumonia, leading to hospitalization, serious complications (such as respiratory failure), and relevant sequalae in childhood and adulthood (wheezing, asthma, and hyperreactive airways). There are no specific clinical signs or symptoms that can distinguish RSV infection from other respiratory pathogens. New multiplex platforms offer the possibility to simultaneously identify different pathogens, including RSV, with an accuracy similar to that of single polymerase chain reaction (PCR) in the majority of cases. At present, the treatment of RSV infection relies on supportive therapy, mainly consisting of oxygen and hydration. Palivizumab is the only prophylactic method available for RSV infection. Advances in technology and scientific knowledge have led to the creation of different kinds of vaccines and drugs to treat RSV infection. Despite the good level of these studies, there are currently few registered strategies to prevent or treat RSV due to difficulties related to the unpredictable nature of the disease and to the specific target population.
PubMed: 33371276
DOI: 10.3390/microorganisms8122048 -
Turk Pediatri Arsivi Jun 2018Respiratory syncytial virus is one of the major causes of respiratory tract infections during infancy with high rates of hospitalization and mortality during the first... (Review)
Review
Respiratory syncytial virus is one of the major causes of respiratory tract infections during infancy with high rates of hospitalization and mortality during the first years of life. It is the most common cause of acute bronchiolitis and viral pneumonia in children below two years of age and second the most common cause of postneonatal infant mortality all around the world following malaria. In addition, the virus has been causally linked to recurrent wheezing and associated with pediatric asthma. The respiratory syncytial virus infections tend to be severe in high risk patients such as patients below six months of age, with prematurity, congenital heart diseases, neuromuscular diseases and immune deficiencies. No specific treatment is available for respiratory syncytial virus infections to date. Severe cases require supportive therapy, mainly oxygen supplementation and hydration, and less frequently, ventilatory support. Because there is no vaccine to prevent respiratory syncytial virus infections or clinically effective treatment to administer to children with respiratory syncytial virus infection, immunoprophylaxis with palivizumab is currently the only method for reducing morbidity associated with severe respiratory syncytial virus in high-risk infants.
PubMed: 30116126
DOI: 10.5152/TurkPediatriArs.2018.6939 -
Human Vaccines & Immunotherapeutics 2014Palivizumab monthly injections throughout the RSV season prevent severe respiratory syncytial virus (RSV) disease in preterm infants ≤ 35 wGA. However, some RSV... (Review)
Review
Palivizumab monthly injections throughout the RSV season prevent severe respiratory syncytial virus (RSV) disease in preterm infants ≤ 35 wGA. However, some RSV guidelines currently recommend stopping palivizumab after 3 months of age in the midst of the RSV season. This article evaluates the need for full-season dosing by reviewing the pharmacokinetic properties of palivizumab and RSV hospitalization (RSVH) risk as a function of chronologic age. Precise human palivizumab protective levels are not established. Clinical trials show significant interpatient variability in palivizumab serum trough concentrations. Partial season dosing is associated with increased risk of RSVH. For late-preterm infants, data suggest that the risk of RSVH remains elevated through at least 6 months of age. Monthly, full-season palivizumab dosing provides the only empirically proven protection from RSVH. In conclusion, late-preterm infants are at significant risk for RSVH through at least 6 months of age and would benefit from dosing throughout the RSV season.
Topics: Antibodies, Monoclonal, Humanized; Antibodies, Viral; Child, Preschool; Humans; Immunization, Passive; Infant; Palivizumab; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Treatment Outcome
PubMed: 24316863
DOI: 10.4161/hv.27426 -
Human Vaccines & Immunotherapeutics Nov 2022Respiratory syncytial virus (RSV) is a leading cause of bronchiolitis and pneumonia in children under one year and a leading cause of infant hospitalization. Palivizumab...
Respiratory syncytial virus (RSV) is a leading cause of bronchiolitis and pneumonia in children under one year and a leading cause of infant hospitalization. Palivizumab was approved by the FDA in 1998 as RSV immunoprophylaxis to prevent severe RSV disease in children with specific health conditions and those born at <35 weeks gestational age (wGA). This study compared RSV-related hospitalization (RSVH) and RSVH characteristics in very preterm (<29 wGA) and term (>37 wGA) infants. Using the MarketScan Commercial and Multi-State Medicaid administrative claims databases, infants born between 7/1/2003 and 6/30/2020 were identified and classified as very preterm or term. Infants with evidence of health conditions, such as congenital heart disease and cystic fibrosis, were excluded. During 2003-2020 RSV seasons (November to March), claims incurred by infants while they were <12 months old were evaluated for outpatient administration of palivizumab and RSVH. The study included 40,123 very preterm infants and 4,421,942 term infants. Rate of RSVH in very preterm infants ranged 1.5-3.8 per 100 infant-seasons in commercially insured infants and 3.5-8.4 in Medicaid insured infants and were inversely related to wGA at birth. Relative risk of RSVH in very preterm was 3-4 times higher, and ICU admissions and mechanical ventilation were more common during RSVH in very preterm infants relative to term infants. However, these outcomes were less common or less severe in very preterm infants who received outpatient palivizumab administration, despite evidence of higher baseline risk of RSVH in these infants.
Topics: Infant; United States; Child; Infant, Newborn; Humans; Palivizumab; Gestational Age; Infant, Premature; Respiratory Syncytial Virus, Human; Respiratory Syncytial Virus Infections; Hospitalization; Infant, Premature, Diseases; Antiviral Agents
PubMed: 36412253
DOI: 10.1080/21645515.2022.2140533 -
Jornal de Pediatria 2023Despite the global impact of the Respiratory Syncytial Virus (RSV) infection in children, only one monoclonal antibody (Palivizumab) has been approved for clinical use.... (Review)
Review
OBJECTIVES
Despite the global impact of the Respiratory Syncytial Virus (RSV) infection in children, only one monoclonal antibody (Palivizumab) has been approved for clinical use. However, advances in the knowledge of RSV immunology may enable the development of safe and effective new vaccines and monoclonal antibodies in a few years. The purpose of this review is to summarize available data on approved and developing passive and active immunizations against RSV in childhood and pregnancy.
DATA SOURCE
A non-systematic review of RSV immunoprophylaxis in childhood and pregnancy was carried out in PubMed, path.org and clinical trial registries, without language restrictions, up to September 2022.
DATA SYNTHESIS
Three monoclonal antibodies and 17 active immunization candidates are under development in phase 1 to 3 clinical studies. Regarding the first group, Nirsevimab is a monoclonal antibody with a prolonged half-life whose approval for clinical use is expected in the next months. Among the vaccines under development, six techniques are being used: protein subunit, viral particles, live attenuated virus, recombinant viral vector, chimeric, and mRNA. The first two approaches are being tested primarily in pregnancy, while the others are being developed for the pediatric population.
CONCLUSIONS
The approval of extended half-life monoclonal antibodies is the next expected advance in RSV prevention, although the costs may be a barrier to the implementation. Regarding active immunizations, maternal and infant vaccination are complementary strategies and there are many promising candidates in clinical studies using different platforms.
Topics: Infant; Pregnancy; Female; Child; Humans; Respiratory Syncytial Virus Vaccines; Palivizumab; Respiratory Syncytial Virus, Human; Respiratory Syncytial Virus Infections; Immunization, Passive; Antibodies, Monoclonal
PubMed: 36402228
DOI: 10.1016/j.jped.2022.10.004 -
International Journal of Molecular... Apr 2021Respiratory syncytial virus (RSV) represents the main cause of acute respiratory tract infections in children worldwide and is the leading cause of hospitalization in... (Review)
Review
Respiratory syncytial virus (RSV) represents the main cause of acute respiratory tract infections in children worldwide and is the leading cause of hospitalization in infants. RSV infection is a self-limiting condition and does not require antibiotics. However hospitalized infants with clinical bronchiolitis often receive antibiotics for fear of bacteria coinfection, especially when chest radiography is performed due to similar radiographic appearance of infiltrate and atelectasis. This may lead to unnecessary antibiotic prescription, additional cost, and increased risk of development of resistance. Despite the considerable burden of RSV bronchiolitis, to date, only symptomatic treatment is available, and there are no commercially available vaccines. The only licensed passive immunoprophylaxis is palivizumab. The high cost of this monoclonal antibody (mAb) has led to limiting its prescription only for high-risk children: infants with chronic lung disease, congenital heart disease, neuromuscular disorders, immunodeficiencies, and extreme preterm birth. Nevertheless, it has been shown that the majority of hospitalized RSV-infected children do not fully meet the criteria for immune prophylaxis. While waiting for an effective vaccine, passive immune prophylaxis in children is mandatory. There are a growing number of RSV passive immunization candidates under development intended for RSV prevention in all infants. In this review, we describe the state-of-the-art of palivizumab's usage and summarize the clinical and preclinical trials regarding the development of mAbs with a better cost-effectiveness ratio.
Topics: Antiviral Agents; Humans; Infant; Palivizumab; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses
PubMed: 33918185
DOI: 10.3390/ijms22073703 -
Current Opinion in Virology Jun 2017Respiratory syncytial virus (RSV) is the most common respiratory pathogen in infants and young children worldwide. Lower respiratory tract infection due to RSV is one of... (Review)
Review
Respiratory syncytial virus (RSV) is the most common respiratory pathogen in infants and young children worldwide. Lower respiratory tract infection due to RSV is one of the most common causes of hospitalization for infants, especially those born premature or with chronic lung or heart disease. Furthermore, RSV infection is an important cause of morbidity in adults, particularly in the elderly and immunocompromised individuals. The acute phase of this infection is often followed by episodes of wheezing that recur for months or years and usually lead to a physician diagnosis of asthma. RSV was discovered more than 50 years ago, and despite extensive research to identify pharmacological therapies, the most effective management of this infection remains supportive care. The trial of a formalin-inactivated RSV vaccine in the 1960s resulted in priming the severe illness upon natural infection. Currently, Palivizumab is the only available option for RSV prophylaxis, and because of restricted clinical benefits and high costs, it has been limited to a group of high-risk infants. There are several ongoing trials in preclinical, Phase-I, Phase-II, or Phase-III clinical stages for RSV vaccine development based on various strategies. Here we review the existing available prophylactic options, the current stages of RSV vaccine clinical trials, different strategies, and major hurdles in the development of an effective RSV vaccine.
Topics: Animals; Antibodies, Monoclonal; Antiviral Agents; Clinical Trials as Topic; Hospitalization; Humans; Immunogenicity, Vaccine; Infant; Mice; Palivizumab; Pre-Exposure Prophylaxis; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus Vaccines; Respiratory Syncytial Virus, Human; Risk Factors; Vaccines, Inactivated
PubMed: 28500974
DOI: 10.1016/j.coviro.2017.03.015 -
Analytica Chimica Acta Jul 2022Full characterization of the attached carbohydrate moieties of glycoproteins is of high importance for both the rapidly growing biopharmaceutical industry and the...
Full characterization of the attached carbohydrate moieties of glycoproteins is of high importance for both the rapidly growing biopharmaceutical industry and the biomedical field. In this paper we report the design and production of three important 6HIS-tagged exoglycosidases (neuraminidase, β-galactosidase and hexosaminidase) to support rapid solid phase N-glycan sequencing with high robustness using immobilized enzymes. The exoglycosidases were generated in bacterial expression systems with high yield. Oriented immobilization via the 6HIS-tag portion of the molecules supported easy accessibility to the active sites and consequently high digestion performance. The three exoglycosidases were premixed in an appropriate matrix format and processed in a low-salt buffer to support long term storage. The digestion efficiencies of the immobilized enzymes were demonstrated by using solid phase sequencing in conjunction with capillary electrophoresis analysis of the products on a commercial glycoprotein therapeutic (palivizumab) and human serum derived fluorophore labeled glycans.
Topics: Electrophoresis, Capillary; Enzymes, Immobilized; Glycoproteins; Glycoside Hydrolases; Humans; Polysaccharides
PubMed: 35680335
DOI: 10.1016/j.aca.2022.339906 -
Frontiers in Immunology 2022Immune escaping from host herd immunity has been related to changes in viral genomic sequences. The study aimed to understand the diverse immune responses to different...
PURPOSE
Immune escaping from host herd immunity has been related to changes in viral genomic sequences. The study aimed to understand the diverse immune responses to different subtypes or genotypes of human respiratory syncytial virus (RSV) in pediatric patients.
METHODS
The genomic sequences of different subtypes or RSV genotypes, isolated from Beijing patients, were sequenced and systematically analyzed. Specifically, the antiviral effects of Palivizumab and the cross-reactivity of human sera from RSV-positive patients to different subtypes or genotypes of RSV were determined. Then, the level of 38 cytokines and chemokines in respiratory and serum samples from RSV-positive patients was evaluated.
RESULTS
The highest nucleotide and amino acid variations and the secondary and tertiary structure diversities among different subtypes or genotypes of RSV were found in G, especially for genotype ON1 with a 72bp-insertion compared to NA1 in subtype A, while more mutations of F protein were found in the NH-2 terminal, including the antigenic site II, the target of Palivizumab, containing one change N276S. Palivizumab inhibited subtype A with higher efficiency than subtype B and had stronger inhibitory effects on the reference strains than on isolated strains. However, RSV-positive sera had stronger inhibitory effects on the strains in the same subtypes or genotypes of RSV. The level of IFN-α2, IL-1α, and IL-1β in respiratory specimens from patients with NA1 was lower than those with ON1, while there were higher TNFα, IFNγ, IL-1α, and IL-1β in the first serum samples from patients with ON1 compared to those with BA9 of subtype B.
CONCLUSIONS
Diverse host immune responses were correlated with differential subtypes and genotypes of RSV in pediatric patients, demonstrating the impact of viral genetics on host immunity.
Topics: Child; Humans; Genotype; Interleukin-1alpha; Palivizumab; Phylogeny; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Immune Evasion
PubMed: 36703972
DOI: 10.3389/fimmu.2022.1084139